scholarly journals From the Clinic to the Laboratory, and Back Again: Investigations on Cannabinoids and Endocannabinoid System Modulators for Treating Schizophrenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Kurt Leroy Hoffman
Keyword(s):  
Animal Models ◽  
Outcome Measures ◽  
Clinical Studies ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Clinical Work ◽  
Clinical Results ◽  
Cognitive Outcome ◽  
Experimental Drugs ◽  
First Results

The present mini-review focuses on animal models of schizophrenia that have explored the effects of cannabidiol (CBD; a non-psychoactive component of cannabis) or the pharmacological manipulation of the endocannabinoid system on behavioral and cognitive outcome measures. First, results of some relevant clinical studies in this area are summarized, and then pre-clinical work on animal models of schizophrenia based on NMDA receptor antagonism or neurodevelopmental manipulations are discussed. A brief overview is given of the theoretical framework on which these models are based, along with a concise summary of results that have been obtained. Clinical results using CBD for schizophrenia seem promising and its effects in animal models of schizophrenia support its potential as a useful pharmacotherapy. Animal models have been paramount for elucidating the actions of CBD and the function of the endocannabinoid system and for identifying novel pharmacological targets, such as cannabinoid receptors and anandamide. However, more attention needs to be placed on defining and applying independent variables and outcome measures that are comparable between pre-clinical and clinical studies. The objective of this review is, on the one hand, to emphasize the potential of such models to predict clinical response to experimental drugs, and on the other hand, to highlight areas in which research on such models could be improved.

scholarly journals Neuroprotective Properties of Cannabinoids in Cellular and Animal Models: Hypotheses and Facts

2020 ◽  
Author(s):  
Lucas D. Udovin ◽  
Andrea Aguilar ◽  
Tamara Kobiec ◽  
María I. Herrera ◽  
Santiago Perez Lloret ◽  
...  
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Cannabinoid Receptors ◽  
Neuronal Loss ◽  
Cholinergic Neurons ◽  
Endocannabinoid System ◽  
Lipid Mediators ◽  
New Drugs ◽  
Memory And Attention ◽  
Neuroprotective Drugs

Progressive neuronal loss is a typical characteristic of neurodegenerative diseases. In Parkinson’s disease, the loss of dopaminergic neurons in the basal ganglia results in impaired mobility and flawed muscle control. The loss of cholinergic neurons largely in the basal forebrain contributes to memory and attention deficits and the overall cognitive impairment in Alzheimer’s disease. This being said, neuroprotective drugs should be expected to preserve and/or restore the functions affected by neuronal loss, and substantially prevent cell death. The endocannabinoid system, comprising lipid mediators able to bind to and activate cannabinoid receptors, has emerged as a therapeutic target of potential interest in a variety of central nervous system diseases. Palmitoylethanolamide (PEA) is one of the most important endocannabinoids, which has a key role in modulating oxidative stress and inflammatory response with neuroprotective potential in neurological disorders. Neurodegenerative diseases undergo varied, progressive stages. The current therapeutical approaches are beginning to fall short when it comes to meet the expected results, urging to either develop or identify or develop new effective treatments. This chapter discusses the neuroprotective potential of new drugs, aiming to shed some light on their proposed mechanism of action and their effect in cellular and animal models of neurodegeneration.

scholarly journals Neuroprotection by Micronutrients and Cannabidiol (CBD) in Neurodegenerative Diseases

2020 ◽  
pp. 1-10
Author(s):  
Kedar N. Prasad ◽  
Kedar N. Prasad
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Neurodegenerative Diseases ◽  
Glutamate Receptors ◽  
Clinical Studies ◽  
Cannabinoid Receptors ◽  
Neurological Diseases ◽  
Endocannabinoid System ◽  
Protective Proteins

The major objectives of this review are to elucidate the role of antioxidants and cannabidiol (CBD) in reducing oxidative stress, inflammation, and glutamate levels, which contribute to the pathogenesis of human neurological diseases. Antioxidants act by: (a) donation of electrons to molecules with unpaired electrons to neutralize them, (b) activation of ROS-resistant Nrf2 to enhance the levels of antioxidant enzymes, (c) restoration of deficiency of antioxidants to normal levels, (d) alterations in the expression of microRNAs, which guide their respective mRNAs to translate protective proteins, and (e) prevention of the release and toxicity of glutamate. CBD acts by: (a) activating endocannabinoid system, which consists of anandamide and archidonoylglycerol, cannabinoid receptors CB1R and CB2R, and their synthesizing and degrading enzymes, (b) acting as an agonist to non-cannabinoid receptors, such as dopamine, serotonin, and adenosine, (c) acting as an inhibitor of serotonin re-uptake, and (d) acting as an antagonist to glutamate receptors. Since antioxidants and CBD act primarily by different mechanisms, it is proposed that combination of the two may be more effective than either individually. No review on this topic has been published. Pre-clinical and clinical studies are suggested to test the efficacy of proposed combination in selected neurodegenerative diseases.

scholarly journals Cannabinoid signalling in embryonic and adult neurogenesis: possible implications for psychiatric and neurological disorders

2018 ◽  
Vol 31 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Rúbia W. de Oliveira ◽  
Cilene L. Oliveira ◽  
Francisco S. Guimarães ◽  
Alline C. Campos
Keyword(s):  
Animal Models ◽  
Adult Neurogenesis ◽  
Neurological Disorders ◽  
Cannabinoid Receptors ◽  
System Development ◽  
Endocannabinoid System ◽  
Qualitative Evaluation ◽  
Nervous System Development ◽  
Cannabinoid Compounds ◽  
Anxiety Depression

AbstractCannabinoid signalling modulates several aspects of brain function, including the generation and survival of neurons during embryonic and adult periods. The present review intended to summarise evidence supporting a role for the endocannabinoid system on the control of neurogenesis and neurogenesis-dependent functions. Studies reporting participation of cannabinoids on the regulation of any step of neurogenesis and the effects of cannabinoid compounds on animal models possessing neurogenesis-dependent features were selected from Medline. Qualitative evaluation of the selected studies indicated that activation of cannabinoid receptors may change neurogenesis in embryonic or adult nervous systems alongside rescue of phenotypes in animal models of different psychiatric and neurological disorders. The text offers an overview on the effects of cannabinoids on central nervous system development and the possible links with psychiatric and neurological disorders such as anxiety, depression, schizophrenia, brain ischaemia/stroke and Alzheimer’s disease. An understanding of the mechanisms by which cannabinoid signalling influences developmental and adult neurogenesis will help foster the development of new therapeutic strategies for neurodevelopmental, psychiatric and neurological disorders.

scholarly journals Endocannabinoid system and pain: an introduction

2013 ◽  
Vol 73 (1) ◽  
pp. 106-117 ◽  
Author(s):  
James J. Burston ◽  
Stephen G. Woodhams
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Clinical Work ◽  
Brain Regions ◽  
Ventrolateral Medulla ◽  
Cannabinoid Type 1 Receptor ◽  
Pain Pathway

The endocannabinoid (EC) system consists of two main receptors: cannabinoid type 1 receptor cannabinoid receptors are found in both the central nervous system (CNS) and periphery, whereas the cannabinoid type 2 receptor cannabinoid receptor is found principally in the immune system and to a lesser extent in the CNS. The EC family consists of two classes of well characterised ligands; the N-acyl ethanolamines, such as N-arachidonoyl ethanolamide or anandamide (AEA), and the monoacylglycerols, such as 2-arachidonoyl glycerol. The various synthetic and catabolic pathways for these enzymes have been (with the exception of AEA synthesis) elucidated. To date, much work has examined the role of EC in nociceptive processing and the potential of targeting the EC system to produce analgesia. Cannabinoid receptors and ligands are found at almost every level of the pain pathway from peripheral sites, such as peripheral nerves and immune cells, to central integration sites such as the spinal cord, and higher brain regions such as the periaqueductal grey and the rostral ventrolateral medulla associated with descending control of pain. EC have been shown to induce analgesia in preclinical models of acute nociception and chronic pain states. The purpose of this review is to critically evaluate the evidence for the role of EC in the pain pathway and the therapeutic potential of EC to produce analgesia. We also review the present clinical work conducted with EC, and examine whether targeting the EC system might offer a novel target for analgesics, and also potentially disease-modifying interventions for pathophysiological pain states.

scholarly journals Role of the Endocannabinoid System in the Central Regulation of Nonmammalian Vertebrate Reproduction

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Erika Cottone ◽  
Valentina Pomatto ◽  
Patrizia Bovolin
Keyword(s):  
Animal Models ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Central Regulation ◽  
Signalling Molecules ◽  
Reproductive Control ◽  
Amphibian Reproduction ◽  
Multiple Levels ◽  
Insight Into

The endocannabinoid system (ECS) has a well-documented pivotal role in the control of mammalian reproductive functions, by acting at multiple levels, that is, central (CNS) and local (gonads) levels. Since studies performed in animal models other than mammals might provide further insight into the biology of these signalling molecules, in the present paper we review the comparative data pointing toward the endocannabinoid involvement in the reproductive control of non-mammalian vertebrates, focussing in particular on the central regulation of teleost and amphibian reproduction. The morphofunctional distribution of brain cannabinoid receptors will be discussed in relation to other crucial signalling molecules involved in the control of reproductive functions, such as GnRH, dopamine, aromatase, and pituitary gonadotropins.

scholarly journals Endocannabinoid System Dysregulation from Acetaminophen Use May Lead to Autism Spectrum Disorder: Could Cannabinoid Treatment Be Efficacious?

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1845
Author(s):  
Stephen Schultz ◽  
Georgianna G. Gould ◽  
Nicola Antonucci ◽  
Anna Lisa Brigida ◽  
Dario Siniscalco
Keyword(s):  
Autism Spectrum Disorder ◽  
Cannabinoid Receptors ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Blood Levels ◽  
Increased Risk ◽  
Patterns Of Behavior ◽  
Arachidonoyl Glycerol

Persistent deficits in social communication and interaction, and restricted, repetitive patterns of behavior, interests or activities, are the core items characterizing autism spectrum disorder (ASD). Strong inflammation states have been reported to be associated with ASD. The endocannabinoid system (ECS) may be involved in ASD pathophysiology. This complex network of lipid signaling pathways comprises arachidonic acid and 2-arachidonoyl glycerol-derived compounds, their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. Alterations of the ECS have been reported in both the brain and the immune system of ASD subjects. ASD children show low EC tone as indicated by low blood levels of endocannabinoids. Acetaminophen use has been reported to be associated with an increased risk of ASD. This drug can act through the ECS to produce analgesia. It may be that acetaminophen use in children increases the risk for ASD by interfering with the ECS.This mini-review article summarizes the current knowledge on this topic.

scholarly journals Pros and Cons of the Cannabinoid System in Cancer: Focus on Hematological Malignancies

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3866
Author(s):  
Natasha Irrera ◽  
Alessandra Bitto ◽  
Emanuela Sant’Antonio ◽  
Rita Lauro ◽  
Caterina Musolino ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Hematological Malignancies ◽  
Antitumor Agents ◽  
Control Cell ◽  
Experimental Studies ◽  
Endocannabinoid System ◽  
Chemotherapeutic Agents ◽  
Cancer Cell Growth ◽  
Cell Functions ◽  
Novel Approach

The endocannabinoid system (ECS) is a composite cell-signaling system that allows endogenous cannabinoid ligands to control cell functions through the interaction with cannabinoid receptors. Modifications of the ECS might contribute to the pathogenesis of different diseases, including cancers. However, the use of these compounds as antitumor agents remains debatable. Pre-clinical experimental studies have shown that cannabinoids (CBs) might be effective for the treatment of hematological malignancies, such as leukemia and lymphoma. Specifically, CBs may activate programmed cell death mechanisms, thus blocking cancer cell growth, and may modulate both autophagy and angiogenesis. Therefore, CBs may have significant anti-tumor effects in hematologic diseases and may synergistically act with chemotherapeutic agents, possibly also reducing chemoresistance. Moreover, targeting ECS might be considered as a novel approach for the management of graft versus host disease, thus reducing some symptoms such as anorexia, cachexia, fatigue, anxiety, depression, and neuropathic pain. The aim of the present review is to collect the state of the art of CBs effects on hematological tumors, thus focusing on the essential topics that might be useful before moving into the clinical practice.

scholarly journals Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3389
Author(s):  
Ishtiaq Ahmed ◽  
Saif Ur Rehman ◽  
Shiva Shahmohamadnejad ◽  
Muhammad Anjum Zia ◽  
Muhammad Ahmad ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Cell Types ◽  
Autoimmune Disorders ◽  
Specific Receptors ◽  
Different Cell Types

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

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